It is known that high blood pressure that is left untreated gives rise to a host of health problems, some of which are heart attacks and strokes. It is not surprising to Dr. Jose Luchsinger of Columbia University Medical Center in New York that high blood pressure (hypertension) can be related to all kinds of cognitive impairment, which is connected to vascular damage in the brain. A cohort study which was published in the December issue of Archives of Neurology included 918 subjects age 65 or older with no history of mild cognitive impairment (MCI) or dementia at baseline. All participants underwent neurophysical and medical testing every 1 ½ years for more than 4 ½ years. The majority of the individuals had high blood pressure. During the course of the study 334 of the participants developed MCI. 174 cases had impairment in domains such as language and executive function or visual-spatial elements were impaired. 160 individuals had amnestic MCI (affecting memory), which is thought to have the strongest link to Alzheimer’s disease.

High Blood Pressure Decreases Cognitive Function

The study showed that hypertension played a significant role in the higher risk of developing any form of cognitive impairment. Detection of hypertension and proper treatment will not only protect against strokes, but certainly also extend its benefits to cognitive function.

In the June 21, 2007 issue of the New England Journal of Medicine a randomized study of 8.7 year duration the question was examined whether postmenopausal women following hysterectomy would have a higher risk with estrogen replacement therapy than controls who did not take estrogen therapy. The lead author was Dr. JoAnn E. Manson of Harvard Medical School and the method chosen to examine the heart disease risk was a CT of the heart to measure calcium in plaque of coronary arteries.

Previous research had shown a good correlation of calcification of coronary arteries with the degree of hardening of coronary arteries as shown in this image.

Various dosages of estrogen were used and overall there was a reduction of calcium scores in all of the groups ranging from 22% to 31% when the calcium scores of the estrogen treated patients were compared to the non treated controls. This translated into 36% to 64% less heart attack rates when the treated groups were compared to the controls not treated with estrogen.

The discussion regarding estrogen replacement therapy following menopause is not finished, but women can be reassured that the cardiovascular risk appears to not be as straight forward as research seemed to suggest in the recent past. There likely was a bias in these retrospective studies and the present prospective study is much stronger having been done over 8.7 years following randomization. As this study was done on patients who had previous hysterectomies, there is no concern about uterine cancer. Breast cancer risk was not examined in this study.

Estrogen In Early Menopause Saves Lives

The authors concluded that low dose estrogen replacement with 0.625mg of conjugated estrogen (Premarine) appears to be safe and has the most beneficial effect on coronary artery health when taken between the ages of 50 and 59. However, the authors also cautioned that estrogen would have multiple effects and may have negative effects on the cardiovascular system in some other way.

Reference: N Engl. J Med. 2007;356:2591-2602

Comment on Nov. 18, 2012: The real problem of this study is that the authors took the wrong “hormone replacement”, namely Premarine, which is a non-bioidentical estrogen concoction from horses, which translates into an ill fitting key. The human body’s estrogen receptors do not fit this “key”. The proper experimental set-up would have been to use bio-identical estrogen hormones, which are usually given as a cream and would be the perfect key for the human estrogen receptors. This would have to be balanced with bio-identical progesterone to achieve a balance the way it is in a younger woman. We know from other studies that this prolongs life by preventing coronary artery disease, prevents Alzheimer’s disease, prevents strokes and does not cause uterine cancer or breast cancer. Women on bio-identical hormone replacement also retain their normal sex drive.

Elderly patients frequently are seen at the doctor’s office because they are “feeling poorly”. Concerned family members mention that there is lack of energy, and mental impairment may also be present. Immediately there may be the question, whether these are symptoms of Alzheimers disease. The other observation may be that the older person is not eating properly. Family physicians will order laboratory tests including vitamin B12 levels. If a deficiency is shown, patients will be advised to take a vitamin supplement, and they may receive injections of vitamin B12.
The unfortunate fact is that vitamin B 12 levels are notoriously unreliable in the diagnosis of deficiency. As early as 1988 a publication in the New England Journal of Medicine showed that neuropsychiatric disorder due to vitamin B12 deficiency can be present in a patient who had normal blood levels and no other findings. It does take some other avenues to detect the deficiency. The blood can be tested for the metabolite called MMA (methylmalonic acid) which is raised with vitamin 12 deficiency. A second test is the measurement of HTC (holotranscobalamin), which is the fraction of vitamin B12 bound to the plasma protein transcobalamin, which delivers the vitamin to the tissues of the body.
Dr. Cherie McCracken and colleagues from the department of psychiatry at Liverpool University, England studied 42 men and 42 women ages 69 to 93.They were tested for cognitive functions like orientation, language, attention and memory. In addition researchers took measurements of the MMA and HTC, the tests mentioned above. None of the test persons had dementia due to the selection criteria, but 31% were cognitively impaired. Mental scores indicating cognitive impairment were associated with increasing age and MMA, and the areas of language comprehension, language expression and ideation practice (translating an idea into an action) were affected.

Check For Vitamin B12 Deficiency In Elderly

The reason for the correlation of MMA with impairment of brain function can be explained by the fact that MMA is toxic to the oxidative function of mitochondria. The process is like a chain reaction: when mitochondria are poisoned, the nerve cells will lack energy for proper function.
Despite this sophisticated interplay of blood levels and cell function in the brain, the message that comes from the researchers is very simple. The MMA has to be ordered as a test in elderly persons, and the next important step is supplementation with vitamin B12 to prevent deterioration in mental functioning.

A recent publication in the medical journal Neurology by Dr. Susan Resnick revealed a surprise link between a lack of testosterone and Alzheimer’s disease.

574 men from the Baltimore Longitudinal Study of Aging who had been followed for about 19 years were analyzed with respect to hormonal factors and their neurological status was also observed. Of these men who ranged in age from 32 to 87 years initially 54 were diagnosed with Alzheimers disease.

When the researchers looked at the hormone status of the men whose mental functioning stayed stable versus those who developed Alzheimers, it was clear that the height of the free testosterone level in the blood (expressed by dividing testosterone by the sex hormone-binding globulin) was a significant predictor for not getting Alzheimers. In other words, if men could maintain a stable level of free testosterone with aging they were significantly protected from Alzheimers disease. The effect was so marked that the blood test could predict 10-years in advance whether a man would develop Alzheimers in future or not. There was a 26% reduction in the risk of Alzheimers with each 10-unit increase in free testosterone.

The same edition of Neurology contains a second report by Dr. Gian Benedetto Melis and coworkers (University of Cagliari, Italy) where around 100 patients (males and females) with Alzheimers were compared with a similar number of patients without Alzheimers. All of their body mass index was in the normal range (20 to 22). These researchers found that the Alzheimers group (both male and female) had an extremely high sex hormone-binding globulin.

Low Testosterone Linked To Alzheimers

The testicles in males and the adrenal glands in males and females can produce testosterone. Dr. Resnick remarked that free testosterone can enter the brain tissue (via the blood brain barrier) easily and act directly on the brain or can be converted to estrogen. Estrogen has been shown in other studies to have a protective effect against Alzheimers. Dr. Resnick cautioned that another study where males with low testosterone levels are getting testosterone supplementation has to be done first before a male should be advised to get treated with testosterone for prevention of Alzheimers disease.

This article is based on a publication by Dr. Resnick et al. in Neurology 2004;62:188-193,301-303.

Comments: It is interesting to note that the “old fashioned” remedies such as weight loss, exercise (particularly anaerobic exercises such as weight training) and a low glycemic diet will naturally increase testosterone levels and vitality in both sexes. A comprehensive program such as the zone diet (by Dr. Barry Sears) or a similar such low glycemic program when combined with exercise will automatically make you lose weight down to a normal body mass index and allow you to maintain it without hunger pangs. It will also normalize hormones in most people on its own as previously elevated insulin levels normalize and the sex hormone-binding globulin will normalize as well. This will make the necessary hormones available to you whether female or male, will prevent osteoporosis (from exercise) and provide enough hormones before and after menopause or andropause to most people. Only a minority of patients will need to get blood tests from their doctors depending on symptoms and those need to seek medical advice to see whether they might benefit from bioidentical hormone replacement therapy.

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Dr. Andreas Papassotiropoulos and his group from the University of Zurich in Switzerland have published an interesting paper in the January issue of archives of Neurology (Arch Neurol 2003;60:29-35). These researchers found when they compared a certain genetic area of 201 patients with Alzheimer’s disease with that of 248 control subjects, that there were important differences in the socalled CYP46 genotype.

A modified form of this genetic region (CYP46*TT genotype) was much more common in the late onset Alzheimers patients than in normal controls. When this test was found to be positive in a patient, this was associated with a 2.16-fold risk of Alzheimers. However, if another known genetic Alzheimers marker (apolipoprotein E epsilon-4) was present also at the same time, the risk of that person having Alzheimers was 9.6-fold when compared to normal controls. With another group of patients who had died from Alzheimers disease, autopsies were done and the brain tissues and cerebrospinal fluids was examined. It was found that the brain tissues and cerebrospinal fluids were loaded with beta-amyloid, which is the glue-like substance typical for Alzheimers.

The Swiss authors concluded from their study that CYP46 is a novel susceptibility gene, which allows to test for Alzheimer’s disease. From other studies it was known that the CYP46 gene encodes the cholesterol 24-hydroxylase, an enzyme that breaks down cholesterol in the brain.

CYP46 Gene Marker Linked With Alzheimers Disease

It was also known that the beta-amyloid is a by-product of this changed cholesterol metabolism in brains of Alzheimers patients. There are now new possibilities of prevention, if perhaps changes in diet would prevent the accumulation of cholesterol in the brain. Also, medications could be developed that help reducing the cholesterol load of Alzheimers brains to prevent the devastating memory loss.